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Fa Ge,
Fanli Zeng,
Na Guo, Junwen Fan,
Yu Song,
Siguo Liu,
Xiuping Wu,
Xuelin Wang,
Xuming Deng,
Qi Jin,
Lu Yu
[show abstract]
[hide abstract]
ABSTRACT: 8-Methoxypsoralen (8-MOP), a naturally occurring furocoumarin found in many plant species, has been reported to have antimycobacterial
activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In the present study, we further test the in vitro synergistic activity of 8-MOP and ethambutol
(EMB), isoniazid (INH), or rifampin (RMP) against M. tuberculosis. This study showed that 8-MOP has antimycobacterial activity against two drug-sensitive and six drug-resistant clinical isolates
of M. tuberculosis, with the minimum inhibitory concentrations of 100–200 and 200–400μg/mL, respectively. A synergistic antimycobacterial effect
between 8-MOP and EMB, INH, or RMP against six drug-resistant strains was observed, with the fractional inhibitory concentration
indices (FICIs) of 0.093–0.156, 0.138–0.285 and 0.093–0.262, respectively. The combination of 8-MOP/EMB, 8-MOP/INH, and 8-MOP/RMP
displayed either synergistic activity or had no interaction when tested against the two clinical drug-sensitive strains and
the standard strain. No antagonism was observed for any drug combination against any of the strains tested. To our knowledge,
this is first report that 8-MOP has synergistic activity with first-line antimycobacterial agents.
KeywordsAntimycobacterial-8-Methoxypsoralen-Mycobacterium tuberculosis-Synergistic
World Journal of Microbiology and Biotechnology 04/2012; 26(4):623-628. · 1.53 Impact Factor
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Na Guo,
Guanghui Ling,
Xiaoying Liang,
Jing Jin, Junwen Fan,
Jiazhang Qiu,
Yu Song,
Ning Huang,
Xiuping Wu,
Xuelin Wang,
Xuming Deng,
Xuliang Deng,
Lu Yu
[show abstract]
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ABSTRACT: Candida albicans is the most common fungal pathogen in humans. The emergence of resistance to azole antifungals has raised the issue of using such antifungals in combination to optimise therapeutic outcome. The objective of this study was to evaluate in vitro synergy of pseudolaric acid B (PAB) and fluconazole (FLC) against clinical isolates of C. albicans. The in vitro antifungal activity of PAB, a diterpene acid from Pseudolarix kaempferi Gordon, was evaluated alone and in combination with FLC against 22 FLC-resistant (FLC-R) and 12 FLC-susceptible (FLC-S) C. albicans using the chequerboard microdilution method and time-killing test assays. Synergism was observed in all 22 (100%) FLC-R strains tested as determined by both fractional inhibitory concentration index (FICI) with values ranging from 0.02 to 0.13 and bliss independence (BI) models. Synergism was observed in two of 12 (17%) FLC-S strains as determined by FICI model with values ranging from 0.25 to 0.5 and in three of 12 (18%) FLC-S strains as determined by BI model. For FLC-R strains, the drug concentrations of FLC and PAB, where synergistic interactions were found, ranged from 0.06 to 4 μg ml(-1) and 0.5 to 4 μg ml(-1) respectively. For FLC-S strains, the drug concentrations of FLC and PAB were 1-8 μg ml(-1) and 0.5-4 μg ml(-1) respectively. The BI model gave results consistent with FICI, but no antagonistic activity was observed in any of the strains tested. These interactions between PAB and FLC were confirmed using the time-killing test for the selected strains. Fluconazole and PAB exhibited a good synergism against azole-R isolates of C. albicans.
Mycoses 09/2011; 54(5):e400-6. · 2.25 Impact Factor
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Fa Ge,
Fanli Zeng,
Siguo Liu,
Na Guo,
Haiqing Ye,
Yu Song, Junwen Fan,
Xiuping Wu,
Xuelin Wang,
Xuming Deng,
Qi Jin,
Lu Yu
[show abstract]
[hide abstract]
ABSTRACT: Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50-100 and 100-200 microg ml(-1), respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121-0.347, 0.113-0.168 and 0.093-0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.
Journal of Medical Microbiology 05/2010; 59(Pt 5):567-72. · 2.50 Impact Factor
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[show abstract]
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ABSTRACT: p-Anisaldehyde (4-methoxybenzaldehyde), an extract from Pimpinella anisum L. seeds, is a potential novel preservative. To reveal the possible action mechanism of p-anisaldehyde against microorganisms, yeast-based commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes in response to p-anisaldehyde. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. We interpreted our microarray data with the clustering tool, T-profiler. Analysis of microarray data revealed that p-anisaldehyde induced the expression of genes related to sulphur assimilation, aromatic aldehydes metabolism, and secondary metabolism, which demonstrated that the addition of p-anisaldehyde may influence the normal metabolism of aromatic aldehydes. This genome-wide transcriptomics approach revealed first insights into the response of Saccharomyces cerevisiae (S. cerevisiae) to p-anisaldehyde challenge.
Journal of Industrial Microbiology 12/2009; 37(3):313-22. · 1.80 Impact Factor
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ABSTRACT: Dictamnine, a natural plant product, has been reported to have antimicrobial activity against bacteria and fungi; however, the dictamnine response mechanisms of microorganisms are still poorly understood. We have shown that dictamnine has antimicrobial activities against the model fungus Saccharomyces cerevisiae, with a minimum inhibitory concentration (MIC) value of 64 microg/ml. Commercial oligonucleotide microarrays were used to determine the global transcriptional response of S. cerevisiae triggered by treatment with dictamnine. We interpreted our microarray data using the hierarchical clustering tool, T-profiler. Several major transcriptional responses were induced by dictamnine. The first was the induced environmental stress response, mainly under the control of the Msn2p and Msn4p transcription factors, and the repressed environmental stress response in genes containing the PAC (RNA polymerase A and C box) and rRPE (ribosomal RNA processing element) motifs. The second was the Upc2p-mediated response involved in lipid biosynthesis. The third comprised the PDR3- and RPN4-mediated responses involved in multidrug resistance (MDR). Finally, the TBP-mediated response was induced with dictamnine treatment. TBP is an essential general transcription factor involved in directing the transcription of genes. Quantitative real-time RT-PCR was performed on selected genes to verify the microarray results. Furthermore, morphological transitions during dictamnine exposure to S. cerevisiae L1190 (MATa/alpha) were examined, using confocal laser microscopy.
Yeast 10/2008; 25(9):631-41. · 1.89 Impact Factor
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ABSTRACT: Some antibacterials have been reported to regulate the host immune and inflammatory responses both in vitro and in vivo. Florfenicol is an antibiotics used in treatment of infection. We investigated the effects of florfenicol on cytokine production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro, and the results showed that florfenicol reduced tumor necrosis factor (TNF) and interleukin-6 (IL-6) production but had little effect on interleukin-1beta (IL-1beta) and interleukin IL-10 (IL-10) secretion. This inspired us to further study the effects of florfenicol in vivo. Florfenicol significantly attenuated TNF and IL-6 production in serum from mice challenged with LPS, and in consistent with the results in vitro. In murine model of endotoxemia, mice were prophylactically or therapeutically treated with florfenicol prior to or after LPS challenge. The results showed that florfenicol significantly increased mouse survival. Further studies revealed that florfenicol prevented the LPS-induced nuclear factor-kappaB (NF-kappaB) translocation from cytoplasm into nuclear in RAW 264.7 macrophages. These observations indicate that florfenicol modulates early cytokine responses by blocking NF-kappaB pathway, and thus, increases mouse survival. This effect of the drug may be of potential usefulness in treatment of bacterial shock.
International Immunopharmacology 08/2008; 8(7):982-8. · 2.38 Impact Factor
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ABSTRACT: Staphylococcus aureus (S. aureus) is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein (RH), a natural plant product, has been reported to have potential antimicrobial activity against S. aureus, but the response mechanisms of S. aureus to RH are still poorly understood. RH showed good in vitro antibacterial activity against all 21 tested S. aureus strains in this experiment. We performed commercial Affymetrix GeneChips to determine the overall transcriptional response of S. aureus ATCC25923 triggered by the treatment of subinhibitory concentrations of RH at one time point 45 min. A total of 88 genes were identified to be differentially regulated by RH. Of these, 28 transporter genes were differentially regulated by RH; RH stress elevated the transcription of genes (srtB and isdABCDEFGI) encoding iron-regulated surface determinants system and genes (nrdIEF and nrdDG) involved in ribonucleotide reductase systems; but RH repressed genes (pflAB, nirBDR, narGH, ldh1, COL-SA0660, COL-SA2363 and COL-SA2386) responsible for anaerobic respiration and fermentation. To our knowledge, this genome-wide transcriptomics approach revealed first insights into the response of S. aureus to RH challenge.
Journal of Biotechnology 07/2008; 135(3):304-8. · 3.05 Impact Factor
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ABSTRACT: In this study, we show that berberine chloride (BBR) has antimicrobial activities against all 43 tested strains of Staphylococcus aureus, an important human and animal pathogen. However, the response mechanisms of S. aureus to BBR are still poorly understood. Affymetrix GeneChips were used to determine the global transcription of S. aureus triggered by treatment with subinhibitory concentrations of BBR. 468 genes were up-regulated and 262 genes were down-regulated upon exposure to BBR. There was elevated transcription of various transporter genes, including genes involved in multidrug resistance, members of the multidrug and toxin extrusion family, the ferrous iron transporter, the amino acid transporter, the Na(+)/H(+) antiporter, and the potassium cation transporter. Measurements of active transport were used to demonstrate a phenotypic correlation between efflux transporter overexpression and inhibition of BBR uptake. Furthermore, BBR induced the expression of urease genes, sortase enzyme, and iron-regulated surface determinant genes, but repressed transcription of a gene encoding arylamine N-acetyltransferase activity (N315-SA2490). To our knowledge, this is the first analysis of a genome-wide transcription profile of S. aureus cells in response to BBR treatment. These results will pave the way to exploring the mechanisms of BBR against S. aureus.
FEMS Microbiology Letters 03/2008; 279(2):217-25. · 2.04 Impact Factor
